Alkylene bis-(oxyalkylene ammonium) compounds



United States Patent ALKYLENE BIS-(OXYALKYLENE ANIMONIUM.) COMPOUNDS Emil Girod, Riehen, near Basel, Switzerland, assignor to J. R. Geigy A. G., Basel, Switzerland, a Swiss company No Drawing. Application June. 8, 1953,

Serial No. 360,360

Claims priority, application Switzerland June :13, 1952 5 Claims. (Cl. 260567.6)

This invention concerns new diammonium compounds of the general formula:

n R .2 A11 wherein R stands for a low molecular alkyl radical,

R represents alkyl radicals each having 5 to carbon m represents a whole number from 2 to 4,

n represents a whole number from 6 to 14, and

An 9 represents a monovalent anion, in particular ,of

halogenhydracids or a normal equivalent .of a polyvalent anion.

Such compounds can be produced by reactingtditertiary m and n have the meanings given above and Ari repre: sents an acid radical corresponding to the anion An' of a halogen hydracid, alkyl sulphuric acid-or aryl sulphonic acid, and if desired, finally exchanging An 9 for another anion.

Compounds in which An 9 is different-from ;An'- 6 i. e. from the anion of a halogen hydracid, alkylsulphuric acid or aryl sulphonic acid, are produced advantageously by later exchange of a halogen ion .for'other anions, by conventional methods.

Insofar as the group in the end product is represented by a low molecular.

can be treated with 2 mols of reactive low molecular alkyl esters of the general formula: v

2,759,020 Patented'iAug. 14, 1956 m vIC Finally. two'mols of tertiary amines of the general formula:

R R-N s R VI can be reacted with -a bis-'halogenalkoxy-alkane of-the general formula:

Hal-(CH2)m,-QT(CH2)n?O(CHz)mHal VlI whereinzHal represents chlorine, bromine or iodine;

The ditertiary'bis-aminoalkoxy-alkanes of the' gen'eral Formula II necessary as starting materialsfor-the general process first named above can be obtained for example by reacting mw-alkane diols of the general formula:

preferably in the form of their metal compounds- (alcoholates) with 2 mols of tertiary aminoalkyl halides of the general formula N- oH, ,,.-Ha1

R or by reacting a.w-dihalogen alkanes of the general formula 7 Hal (CHz nHal with. v2 molsrof stertiaryaminoalcohols of the general f rmul 'N c-H,);,;-ori -R "@150 advantageously in the form of their metal compounds; The secondprocess to be preferred when the correspondingtertiary:aminoalkyl halides which are necessary in the first process arevery instable, such as e. g. for the productiontof ditertiaryIbis-(6-aminobutoxy)-al- ,lganes; It is also vpossible-however, to react the bishalogenalkoxyalkanes of the general formula 1 VII with secondary amines of the general formula:

instead of with tertiary amines inorder to obtain the ditertiary bis-aminoalkoxyalkanes of the general Formula II.

The following can be named for example i as ,ditertiary bis-aminoalkoxy-alkanes 1.6 bis (,8 dimethylamino ethoxy) hexane, B. P.12

l.6-bis-('y-dimethylarnino-propoxyfihexane, B. P.o.oa 119- 1.6-bis-(' -dimethylamino-propoxy)hexane,B. 1 .0.63 119- 1.6-bis-(' -diethylaminowprppoxy) -hexane, B. P.o.o3 133- 1.6 bis dibutylamino propoxy) hexane, B. P.0.o4

1.6 bis (6 dimethylamino butoxy) hexane, B.'P.o.os

1.6 bis (5 diethylamino-s butoxy) t-hexaneyB. Pm-1 1.6 bis (/3 dimethylamino ethoxy-)"- 3 methyl-hexane; 'B. 110.09 1l4 1l5,

1.7-bis-(fl-dimethylamino-ethoxy)-heptane, B. Ron's-138- 1;8 bis (B dimethylamino 4 ethoxy-)'--'octane B. P-.u.os

1.8 bis (13 diethylamino ethoxy) octane, B. P.o.oa

1.8-bis-('y-diethylamino-propoxy) -octane, B. P.o.05 163- 1.9 bis (,B dimethylamino ethoxy) nonane,.B. P.o.os

1.9 bis (13 diethylamino ethoxy) nonane, B. P. 0.0:;

1.10 bis (B dimethylamino ethoxy) decane, B. P.o.o4

1.10-bis -diethylarninoapropoxy)-decane, B. P.o.03 164- 169, 1.10-bis-(' -dibutylamino-propoxy)-decane, B. P.o.09 230- 1.11 bis (,8 dimethylamino ethoxy) undecane,

B. P.o.1s about 152, 1.12 bis ('y diethylamino propoxy) dodecane,

B. P.o.oo1 about 130, 1.14 bis (e diethylamino ethoxy) tetradecane,

B. P.n.0o1 about 170175.

In particular the halides as well as sulphuric acid and aryl sulphonic acid esters can be used as reactive alkyl esters of the general formula RAm.

As examples can be named: 2-amyl chloride, bromide and iodide, isoamyl, 2-methyl-butyl-, 2.2-dimethyl-propyl-, n-hexyl-, isohexyl-, 2-methyl-pentyl-, 3-methyl-pentyl-, n-heptyl-, n-octyl-, 2-ethyl-hexyl-, n-nonyl-, and n-decylchloride, -bromide and iodide.

If, in the processes given above for the production of ditertiary bis-aminoalkoxy-alkanes, compounds are used as starting materials which contain a mixed dialkylamino group instead of the low molecular dialkylamino group, starting materials are obtained in an analogous manner for the second general process given above for the production of the diammonium compounds, e. g. 1.10-bis- [,B-(n-amyl-methylamino)-ethoXy]-decane or 1.10-bis ['y- (isoarnyl-methylarnino)-propoxy]-decane. These compounds are obtained by reacting for example, tertiary aminoalkyl halides of the general formula N-(CHa) --Hal with metal compounds of a.w-alkane diols or by reacting tertiary amino alcohols of the general formula with a.w-di.hal0gen 'alkanes; also mixed dialkylamines of alkanes ofthe general formula IV or the desired diammonium compounds in general formula I can be obtained in one process without isolating the above named ditertiary intermediate products.

As reactive loW molecular alkyl esters which can be reacted with bis-(dialkylamino-alkoxy)-alkanes (IV) according to the second general process can be named for example, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, propyl bromide, propyl iodide, butyl bromide, butyl iodide, isobutyl bromide, hexyl bromide, allyl bromide and allyl iodide as Well as dimethyl sulphate, diethyl sulphate and p-toluene-sulphonic acid methyl ester.

The bis-halogenalkoxy-alkanes of the general formula VII which are starting materials for the third general process for the production of the new diammonium compounds, such as 1.2-bis-(5-bromobutoxy)-ethane, can be obtained for example by reacting bis-(hydroxy-alkoxy)- alkanes with phosphorus halides. Bis-hydroxyalkoxyalkanes can be obtained for example by reacting 0:.wdihalogen alkanes with excess u.w-alkane diols by means of sodium. The tertiary substituted amines which are necessary as second reaction component in this process are easily obtained e. g. by reacting alkyl halides with the corresponding secondary amines.

The diammonium compounds produced according to the present invention can be used for pharmaceutical purposes. In particular they influence the muscle tonus, in that they exert a muscle relaxing action similar to curare.

The following examples illustrate the invention further. Parts are given as parts by weight, preferably in grammes. The relationship of parts by Weight to parts by volume is as that of grammes to cubic centimetres. The temperatures are in degrees-Centigrade.

Example 3.16 parts ofl.10-bis-(p-dimethylamino-ethoxy)-decane crystallising from a little abs. methanol with the addition a of butanone, it melts at 182.

1.10-bis- [B-(n-hexyl-dimethyl-ammoniub)ethoxy] decane-dibromide (M. P. is obtained in an analogous way if 3.8 parts of n-hexyl bromide are used.

Similarly 1.9-bis- [fl-(n-hexyl dimethyl ammonium)- ethoxy] nonane-dibromide is obtained from 3.02 parts of 1.9-bis-(fl-dimethylamino-ethoxy)-nonane and 3.8 parts of hexyl bromide. M. P. 122124.

The following can be produced in an analogous manner, e. g.

1.6-bis- [fl- (n-amyl-dimethyl-ammonium) -ethoxy] -hexanedichloride,

1.6-bis-[' -(n-hexyl-dimethyl-ammonium) propoxy1hexane-dimethosulphate,

1.7-bis- [fi-(isoamyl-dimethyl-ammonium)-ethoxyl heptame-dichloride,

1.6-bis- [B-(n-amyl-dimethyl-ammonium) -ethoxy] -3 -methyl hexane hexane-dibromide,

1 .8-bis- [fl- (isoamyl-dimethyl-ammonium) -ethoxy] -octanedichloride 1.9-bis- [fi-(n-amyl-dimethyl-ammonium) ethoxy] -nonauedichloride,

1.IO-bis-[,8-(n-amyl-dimethyl-ammonium) ethoxy] decane-dibromide,

1.10-bis- [fi-(n-octyl-dimethyl-ammonium) ethoxy] decane-di-iodide,

1.10-bis- [B-(n-heptyl-dimethylammonium) ethoxy] decane-dibromide,

1.10-bis-[fl-(isoamyl-dimethyl-ammonium)-ethoxy) decane-dichloride,

1.10-bis-[fi-(n-hexyl-diethyl-ammonium)-ethoxy]-decanedi-iodide,

10.10-bis-['y(n-amyl-dimethyl-ammonium)-propoxy] decane-dibromide,

1.10-bis- -(isoamyl-dibutyl-ammonium') -propoxy] decane-dibromide,

1.10-bis-[6(n-amyl-dimethyl-ammonium) -butoxy1 decane-dibromide,

1.1 l-bis- [5-(isoamyl-dimethyl-ammonium) -ethoxy] -undecane-dichloride,

1.1l-bis-[p3-(n-hexyl-methyhethyl-ammonium) etholxylundecane-dibromide,

1. 12-bis- [/3-( -n-amyl-dimethyl-amrnonium) -ethoxy] -dodecane-dichloride,

1.12-bis-[fi-(isoamyl-diethyl-ammonium)-ethoxy] dodecane-dichloride,

1.12-bis- [13-(n-amyl-dipropyl-ammonium)-ethoxy] dodecane-dibromide,

1.13-bis-[,8-(isoamyl-dimethyl-ammonium)-ethoxy] tridecane-dichloride,

1 14-bis- [p-(n-hexyl-dimethyl-ammonium) -ethoxy] -tetradecane-di-iodide,

1.14-b1's- [B- (n-omyl-diethyl-ammonium) -ethoxy] -tetradecane-dibromide. What I claim is: 1. A diammonium compound of the formula wherein R stands for a low molecular alkyl radical,

R represents an alkyl radical having 5 to 10 carbon atoms, m represents an integer from 2 to 4,

n represents an integer from 6 to 14, and

A119 represents a therapeutically useful monovalent anion.

2. A diammonium compound of the formula CH5;NCH:-CHx-O(CH3)10-O-CHr-CHg-N-CH; CH, CH: -2 13:

References Cited in the file of this patent UNITED STATES PATENTS 2,683,147 Girod July 6, 1954 FOREIGN PATENTS 511,220 Belgium May 31, 1952 841,917 Germany June 19, 1952 OTHER REFERENCES Unna et 211., Annals of the New York Academy of Sciences 54, (Art. 3) 425, Oct. 30, 1951.

Girod et al., Experientia 8, 233-34 (1952). 

1. A DIAMMONIUM COMPOUND OF THE FORMULA WHEREIN R STANDS FOR A LOW MOLECULAR ALKYL RADICAL, R'' REPRESENTS AN A ALKYL RADICAL HAVING 5 TO 10 CARBON ATOMS, M REPRESENTS AN INTERGER FROM 2 TO 4, N REPRESENTS AN INTEGER FROM 6 TO 14 AND AN $ REPRESENTS A THERAPEUTICALLY USEFUL MONOVALENT ANION. 